Experimental and molecular pathology最新文献_第3页

Maternal lung inflammation and apoptosis following gestational exposure to secondhand smoke and E-cigarette vapor: Implications for maternal-fetal health 妊娠期暴露于二手烟和电子烟蒸汽后的母体肺部炎症和细胞凋亡：对母胎健康的影响

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2026-03-01 Epub Date: 2026-01-20 DOI: 10.1016/j.yexmp.2026.105026

Olivia Hiatt, Benjamin D. Davidson, Logan Beck, Katelyn A. Sturgis, Ethan Evans, Elizabeth Thurmond, Madeline Boyer, Benjamin T. Bikman, Paul R. Reynolds, Juan A. Arroyo

Pregnancy is a vulnerable period where maternal exposure to environmental toxicants like secondhand smoke (SHS) and electronic cigarette (eCig) aerosols can harm maternal and fetal health. This study examines the differential impacts of SHS and eCig exposure on maternal lung tissue during late gestation, focusing on inflammation, apoptosis, and oxidative stress. Pregnant C57BL/6 mice were exposed to SHS or eCig aerosols for four or six days from embryonic day 12.5 or 14.5, with lung tissues collected on day 18.5 for analysis. Bronchoalveolar lavage fluid and lung tissue were assessed for inflammation, apoptosis, and oxidative stress. SHS exposure caused pronounced immune activation and mitochondrial-mediated apoptosis, while eCig exposure induced a milder inflammatory response with evidence of epithelial remodeling and oxidative imbalance. Collectively, both exposures disrupted maternal pulmonary homeostasis, with SHS producing stronger inflammatory effects. Unlike SHS, eCig exposure caused transient apoptosis with partial preservation of anti-apoptotic pathways (Bcl-2, IGF-1), while SHS exhibited stronger pro-inflammatory effects, eCig exposure still contributed to oxidative stress and immune dysregulation. These findings underscore the risks of both exposures during pregnancy, emphasizing the need for stringent public health policies regulating eCig use to protect maternal and fetal health.

怀孕是一个脆弱的时期，母亲接触二手烟（SHS）和电子烟（eCig）气溶胶等环境有毒物质会损害母亲和胎儿的健康。本研究探讨了妊娠后期SHS和eCig暴露对母体肺组织的不同影响，重点关注炎症、细胞凋亡和氧化应激。妊娠C57BL/6小鼠从胚胎第12.5天或14.5天开始暴露于SHS或eCig气溶胶中4天或6天，并在第18.5天收集肺组织进行分析。评估支气管肺泡灌洗液和肺组织的炎症、细胞凋亡和氧化应激。SHS暴露引起明显的免疫激活和线粒体介导的细胞凋亡，而eCig暴露引起较轻的炎症反应，并伴有上皮重塑和氧化失衡。总的来说，这两种暴露都破坏了母体肺内平衡，其中SHS产生更强的炎症作用。与SHS不同的是，eCig暴露导致短暂性细胞凋亡，并部分保留抗凋亡通路（Bcl-2, IGF-1），而SHS表现出更强的促炎作用，eCig暴露仍导致氧化应激和免疫失调。这些发现强调了怀孕期间两种暴露的风险，强调需要制定严格的公共卫生政策来规范eCig的使用，以保护母亲和胎儿的健康。

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引用次数: 0

Metixene hydrochloride hydrate mitigates kidney tubulointerstitial fibrosis by inhibiting Smad3 phosphorylation 盐酸水合美替昔通过抑制Smad3磷酸化减轻肾小管间质纤维化

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2026-03-01 Epub Date: 2026-01-16 DOI: 10.1016/j.yexmp.2026.105025

Kyeong-Min Lee , Yeo Jin Hwang

Chronic Kidney disease (CKD), in which renal fibrosis is the defining pathological feature, poses significant global health and economic challenges. Despite its high clinical prevalence, effective therapies to prevent or reverse renal fibrosis remain scarce. Metixene hydrochloride hydrate (MHH), an anticholinergic drug once used for Parkinson's disease, has not been evaluated for renal fibrosis. Here, we investigated whether MHH mitigates renal fibrosis in a unilateral ureteral obstruction (UUO) mouse model and evaluated its effects on transforming growth factor-β1 (TGF-β1) signaling in renal cells. MHH did not affect the cell viability of NRK-49F cells at concentrations ranging from 0.5 to 5 μM. In vitro, MHH effectively suppressed TGF-β1-induced PAI-1 expression (both mRNA and protein) and secretion in renal fibroblasts, as well as PAI-1 secretion and protein expression in renal glomerular endothelial cells. Furthermore, TGF-β1 stimulated the mRNA and protein expressions of key renal fibrotic factors, including collagen type I, fibronectin, and alpha-smooth muscle actin, in NRK-49F cells. MMH significantly inhibited the expression of these renal fibrotic factors in these cells. UUO kidneys exhibited markedly increased tubular atrophy and interstitial fibrosis, as well as increased expression of renal fibrotic markers. MHH treatment significantly mitigated these pathological parameters and expression of renal fibrotic markers. Mechanistically, MHH suppressed TGF-β1-induced Smad3 phosphorylation both in vitro and in vivo. Our findings indicate that MHH exerts potent antifibrotic effects by downregulating the TGF-β1/Smad3 signaling pathway and suppressing the expression of fibrotic factors in renal cells and obstructed kidneys. Therefore, MHH could be repositioned as a therapeutic agent for renal fibrosis in various kidney diseases.

慢性肾脏疾病（CKD），其中肾纤维化是定义的病理特征，造成重大的全球健康和经济挑战。尽管其临床患病率很高，但预防或逆转肾纤维化的有效疗法仍然很少。盐酸水合美替昔（MHH）是一种抗胆碱能药物，曾用于帕金森病，但尚未对其治疗肾纤维化进行评估。本研究在单侧输尿管梗阻（UUO）小鼠模型中研究MHH是否减轻肾纤维化，并评估其对肾细胞中转化生长因子-β1 （TGF-β1）信号传导的影响。在0.5 ~ 5 μM浓度范围内，MHH对NRK-49F细胞活力无影响。在体外，MHH能有效抑制TGF-β1诱导的肾成纤维细胞中PAI-1 mRNA和蛋白的表达和分泌，以及肾小球内皮细胞中PAI-1的分泌和蛋白表达。TGF-β1刺激NRK-49F细胞中I型胶原、纤维连接蛋白、α -平滑肌肌动蛋白等关键肾纤维化因子的mRNA和蛋白表达。MMH显著抑制这些肾纤维化因子在这些细胞中的表达。UUO组肾小管萎缩和间质纤维化明显增加，肾纤维化标志物表达增加。MHH治疗显著减轻了这些病理参数和肾纤维化标志物的表达。在机制上，MHH在体外和体内均抑制TGF-β1诱导的Smad3磷酸化。我们的研究结果表明，MHH通过下调TGF-β1/Smad3信号通路，抑制肾细胞和梗阻肾中纤维化因子的表达，发挥有效的抗纤维化作用。因此，MHH可以重新定位为各种肾脏疾病的肾纤维化治疗剂。

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引用次数: 0

Understanding diabetes and its complications through the lens of Drosophila 通过果蝇的视角了解糖尿病及其并发症。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2026-03-01 Epub Date: 2025-12-15 DOI: 10.1016/j.yexmp.2025.105017

Supriya Bevinakoppamath , Anju Srinivas , Chandan Gowda Umesha , Akila Prashant , Amanjot Singh , Vinay Kumar Rao

A significant gap exists between preclinical findings in animal models and their translation to diabetes therapeutics. Although several generic drugs are currently available, an effective and precise control of glycemia is challenging, and side effects due to both hyperglycemia and drugs are common. This is partly due to our incomplete understanding of disease mechanisms. It is now appreciated that, due to its simplicity and well-conserved genetic pathways, Drosophila disease modeling is an excellent choice for studying diabetes and its complications. Here, we review knowledge about conserved glucose sensing mechanisms, energy homeostasis pathways, and diabetes modeling in Drosophila. We discuss how hyperglycemia-induced metabolic deregulations cause diabetic complications. Further through the lens of Drosophila, we highlight molecular mechanisms underlying vascular and emerging diabetic complications, including neurodegeneration and cancer. We conclude with the thought that diabetes modeling in Drosophila could prove beneficial in large-scale screening of drugs for diabetes and its complications.

动物模型的临床前研究结果与其转化为糖尿病治疗方法之间存在显著差距。虽然目前有几种仿制药可用，但有效和精确控制血糖是具有挑战性的，而且由于高血糖和药物引起的副作用是常见的。这部分是由于我们对疾病机制的理解不完整。现在人们认识到，由于果蝇疾病模型的简单性和保守的遗传途径，果蝇疾病模型是研究糖尿病及其并发症的一个很好的选择。在这里，我们回顾了关于果蝇的保守葡萄糖传感机制、能量稳态途径和糖尿病建模的知识。我们讨论了高血糖引起的代谢失调如何引起糖尿病并发症。进一步通过果蝇的透镜，我们强调血管和新出现的糖尿病并发症的分子机制，包括神经变性和癌症。我们的结论是，果蝇的糖尿病模型可能有助于糖尿病及其并发症药物的大规模筛选。

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引用次数: 0

Exploring the characteristics of the SKP2-CDK6 axis in pancreatic cancer cell metastasis and its clinical significance 探讨SKP2-CDK6轴在胰腺癌细胞转移中的特征及其临床意义

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2026-03-01 Epub Date: 2026-01-13 DOI: 10.1016/j.yexmp.2026.105024

Hui-Ching Wang , Chi-Wen Luo , Sin-Hua Moi , Ya-Hui Chang , Shu-Jyuan Chang , Yu-Hsuan Hung , Tzu-Yi Chen , Yi-Zi Chen , Chiao-Ying Lai , Yu-Ci Yang , Chun-Chieh Wu , Li-Tzong Chen , Mei-Ren Pan

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic malignancy with limited biomarkers for early detection. Recurrence and metastasis after surgical resection remain major causes of mortality, highlighting the urgent need for novel therapeutic strategies.

Methods

We integrated clinical database analyses and functional assays in PDAC cell lines and mouse models to investigate the role of the SKP2-CDK6 axis in tumor progression, metastasis, and gemcitabine resistance.

Results

Elevated CDK6 expression correlated with poorer progression-free and overall survival in PDAC patients and was associated with advanced stage and lymph node metastasis. SKP2 expression positively correlated with CDK6, and mechanistic studies revealed that SKP2 may transcriptionally regulate CDK6. Inhibition of CDK6 suppressed tumor growth and metastasis in vitro and in vivo, and reduced epithelial-mesenchymal transition. Combining a CDK6 inhibitor with gemcitabine significantly reduced colony formation in gemcitabine-resistant PDAC cells, suggesting a synergistic anticancer effect.

Conclusions

The SKP2-CDK6 axis may drive PDAC progression and chemoresistance. Co-targeting SKP2 and CDK6 in combination with gemcitabine may represent a promising therapeutic approach, warranting further preclinical and clinical evaluation to improve outcomes for patients with PDAC.

胰腺导管腺癌（PDAC）是一种高度转移的恶性肿瘤，早期检测的生物标志物有限。手术切除后的复发和转移仍然是导致死亡的主要原因，因此迫切需要新的治疗策略。方法结合PDAC细胞系和小鼠模型的临床数据库分析和功能分析，探讨SKP2-CDK6轴在肿瘤进展、转移和吉西他滨耐药中的作用。结果CDK6表达升高与PDAC患者较差的无进展生存期和总生存期相关，并与晚期和淋巴结转移相关。SKP2表达与CDK6呈正相关，机制研究表明SKP2可能通过转录调控CDK6。抑制CDK6抑制肿瘤生长和体内转移，减少上皮-间质转化。CDK6抑制剂与吉西他滨联合可显著减少耐吉西他滨PDAC细胞的集落形成，提示协同抗癌作用。结论SKP2-CDK6轴可能驱动PDAC进展和化疗耐药。联合吉西他滨联合靶向SKP2和CDK6可能是一种很有前景的治疗方法，需要进一步的临床前和临床评估来改善PDAC患者的预后。

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引用次数: 0

Regulatory role of protein tyrosine phosphatases in hematopoiesis and leukemogenesis 蛋白酪氨酸磷酸酶在造血和白血病发生中的调节作用。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2026-03-01 Epub Date: 2026-03-02 DOI: 10.1016/j.yexmp.2026.105033

Xiaoting Wang , Yuyao Guan , Yizhuo Qin , Zhen Guan , guangsen Xu , Yining Dong , Zhiyuan Lu , Xiuling Zhang , Lei Zheng , Qian Zhou

Protein tyrosine phosphatases (PTPs), pivotal regulators of tyrosine phosphorylation dynamics, orchestrate cellular signaling networks to govern fundamental processes such as hematopoietic stem cell (HSC) quiescence, proliferation, and stress responses. Dysregulation of PTPs disrupts tyrosine phosphorylation homeostasis, culminating in HSC dysfunction, malignant transformation and leukemogenesis through aberrant activation of oncogenic pathways. This review summarizes the recent advances in understanding PTP-mediated mechanisms underlying HSC maintenance and leukemogenesis, with a focus on their dual roles as tumor suppressors and context-dependent oncogenic drivers. It could help explore the molecular mechanism of normal hematopoietic homeostasis and provide potential therapeutic targets of the related blood diseases.

蛋白酪氨酸磷酸酶（PTPs）是酪氨酸磷酸化动力学的关键调节因子，协调细胞信号网络来控制造血干细胞（HSC）静止、增殖和应激反应等基本过程。ptp的失调会破坏酪氨酸磷酸化的稳态，最终通过异常激活致癌途径导致HSC功能障碍、恶性转化和白血病的发生。本文综述了ptp介导的HSC维持和白血病发生机制的最新进展，重点介绍了ptp作为肿瘤抑制因子和环境依赖性致癌驱动因子的双重作用。这有助于探索正常造血稳态的分子机制，为相关血液病的治疗提供潜在的靶点。

引用次数: 0

Expression of concern: “LncRNAs and miRNAs participate in determination of sensitivity of cancer cells to cisplatin” [Experimental and Molecular Pathology 123 (2021) 104602] 关注表达：“LncRNAs和miRNAs参与确定癌细胞对顺铂的敏感性”[实验与分子病理学123 (2021)104602]

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2026-01-01

引用次数: 0

Expression of concern: “The critical roles of lncRNAs in the pathogenesis of melanoma” [Experimental and Molecular Pathology 117 (2020) 104558] 关注表达：“lncRNAs在黑色素瘤发病机制中的关键作用”[实验与分子病理学117 (2020)104558]

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2026-01-01

引用次数: 0

Breaking barriers: Innovative therapies for managing homozygous familial hypercholesterolemia 突破障碍：管理纯合子家族性高胆固醇血症的创新疗法。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-12-01 Epub Date: 2025-10-16 DOI: 10.1016/j.yexmp.2025.105003

Shuai-Jie Huang , Ping Huang , Nan-Nan Song , Xian-Hui Jia , Hong-Li Gao , Zhi-Yuan Lu , Xiao-Lan Wen

Homozygous familial hypercholesterolemia (HoFH) is a rare autosomal recessive disorder characterized by variants in genes involved in the regulation of low-density lipoprotein cholesterol (LDL-C) metabolism. The genetic basis of HoFH is complex, with biallelic variants in the low-density lipoprotein receptor (LDLR) gene being the most prevalent. Early diagnosis and appropriate lipid-lowering therapy (LLT) are essential for patients with HoFH to prevent the premature onset of atherosclerotic cardiovascular disease (ASCVD). Effective and timely reduction of LDL-C levels is crucial for the success of LLT. Nevertheless, the majority of patients with HoFH exhibit resistance to conventional LLT due to insufficient or absent activity of LDL-R, rendering the management of HoFH challenging. Recent advancements have introduced novel pharmacological agents for treating HoFH (e.g. evolocumab, alirocumab, inclisiran and bempedoic acid), including cholesterol-lowering strategies that function independently of LDL-R such as lomitapide and evinacumab offering significant promise for managing this condition. However, disparities in the treatment of HoFH persist across different regions and countries. In this context, the review provides a comprehensive overview of established treatment modalities and emerging therapeutic agents for individuals with HoFH.

纯合子家族性高胆固醇血症（HoFH）是一种罕见的常染色体隐性遗传病，其特征是参与调节低密度脂蛋白胆固醇（LDL-C）代谢的基因变异。HoFH的遗传基础是复杂的，低密度脂蛋白受体（LDLR）基因的双等位变异是最普遍的。早期诊断和适当的降脂治疗（LLT）对于HoFH患者预防早发的动脉粥样硬化性心血管疾病（ASCVD）至关重要。有效及时的降低LDL-C水平是LLT成功的关键。然而，由于LDL-R活性不足或缺失，大多数HoFH患者表现出对常规LLT的耐药性，这使得HoFH的治疗具有挑战性。最近的进展已经引入了治疗HoFH的新型药物（如evolocumab， alirocumab， inclisiran和bempedoic acid），包括独立于LDL-R起作用的降胆固醇策略，如lomitapide和evinacumab，为治疗这种疾病提供了重要的希望。然而，不同地区和国家在治疗HoFH方面仍然存在差异。在此背景下，本综述全面概述了HoFH患者的现有治疗方式和新兴治疗药物。

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引用次数: 0

Celecoxib and naproxen disrupt autophagy and activate EGR1 in kidney tubules 塞来昔布和萘普生破坏自噬并激活肾小管中的EGR1

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI: 10.1016/j.yexmp.2025.105000

Samaneh Haghighi , Arezoo Haghighi , Zoltán S. Zádori , Krisztián Kovács , Anna Manzéger , Gábor Kökény

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic effects, although the possible COX-independent impact on the kidneys is largely unknown. Kidney damage is often associated with defective autophagy and autophagy dysregulation has been associated with kidney fibrosis and the pro-fibrotic EGR1 transcription factor activation. The non-selective COX inhibitor indomethacin (IND) can be nephrotoxic, but the impact of selective COX-2 inhibitor celecoxib (CEL) or the non-selective naproxen (NAP) on renal autophagy and EGR1 remain obscure. Here, we investigated the dose-dependent effect of CEL and NAP administration on human proximal tubule epithelial (HK-2) cells and murine inner medullary collecting duct (IMCD) cells in comparison to the effects of IND. To elucidate chronic renal effects, we also treated rats similarly for two weeks. We found that high doses of CEL and NAP, but not IND, disrupted autophagy, increased oxidative stress, and activated pro-fibrotic pathways in both HK-2 and IMCD cells with induced EGR1, accompanied by ACTA2 upregulation. We found similar effects in the renal medulla of rats treated with high-dose CEL and NAP. In addition, autophagy dysfunction was evident through increased LC3-II/I and p62 accumulation. Histology confirmed dose-dependent tubular damage and nuclear EGR1 accumulation in CEL and NAP treated rats, accompanied by induced HMOX1 and AKT phosphorylation. Our study reveals dose-dependent tubulotoxic effects of NSAIDs unrelated to their COX-selectivity, suggesting an interplay between pro-fibrotic transcription factor EGR1, autophagy pathways and oxidative stress. These findings underscore the need for meticulous dose optimization especially in kidney disease patients in order to reduce nephrotoxicity.

非甾体抗炎药（NSAIDs）因其镇痛作用而被广泛使用，尽管对肾脏可能的cox非依赖性影响在很大程度上是未知的。肾损伤通常与自噬缺陷有关，自噬失调与肾纤维化和促纤维化EGR1转录因子激活有关。非选择性COX抑制剂吲哚美辛（IND）可能具有肾毒性，但选择性COX-2抑制剂塞来昔布（CEL）或非选择性萘普生（NAP）对肾自噬和EGR1的影响尚不清楚。在这里，我们研究了CEL和NAP给药对人近端小管上皮细胞（HK-2）和小鼠髓内集管（IMCD）细胞的剂量依赖性作用，并与IND的作用进行了比较。为了阐明慢性肾脏作用，我们也对大鼠进行了两周的类似治疗。我们发现，高剂量的CEL和NAP，而不是IND，在诱导EGR1的HK-2和IMCD细胞中破坏自噬，增加氧化应激，激活促纤维化途径，并伴有ACTA2上调。我们发现高剂量CEL和NAP对大鼠肾髓质的影响相似。此外，自噬功能障碍明显通过LC3-II/I和p62积累增加。组织学证实了CEL和NAP处理大鼠的剂量依赖性小管损伤和核EGR1积累，并伴有诱导的HMOX1和AKT磷酸化。我们的研究揭示了非甾体抗炎药的剂量依赖性小管毒性作用与其cox选择性无关，表明促纤维化转录因子EGR1、自噬途径和氧化应激之间存在相互作用。这些发现强调需要细致的剂量优化，特别是在肾脏疾病患者，以减少肾毒性。

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引用次数: 0

Prospective evaluation of copy number alterations validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma 拷贝数改变的前瞻性评估验证了染色体1q增益是局部尤文氏肉瘤预后不良的独立标志。

IF 3.7 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-12-01 Epub Date: 2025-11-17 DOI: 10.1016/j.yexmp.2025.105008

Juan Díaz-Martín , Andreas Ranft , Maite Blanquer-Maceiras , Rosa Noguera , Carmen Salguero-Aranda , Daniel Delgado-Bellido , Laura Romero-Pérez , Uta Dirksen , Enrique de Álava

Background

Ewing sarcoma is a rare and aggressive tumor affecting mainly adolescents and young adults. Accurate risk stratification is critical for treatment tailoring, yet traditional clinical parameters lack sufficient predictive accuracy. While retrospective studies have identified potential molecular biomarkers, prospective validation is required for clinical implementation.

Methods

The international PROVABES consortium (PROspective Validation of Biomarkers in Ewing Sarcoma) aims to evaluate molecular prognostic markers in European patients treated under international phase III trials. This study focuses on copy number alterations (CNAs), in 305 primary tumors. Tissue microarrays were analyzed by FISH for chromosome 1q gain (n = 297) and 16q loss (n = 266). Genome-wide CNAs were further assessed using SNP arrays in 139 samples. Associations with clinical outcomes were evaluated via Kaplan-Meier and multivariate Cox regression, with event-free survival (EFS) and overall survival (OS) as endpoints.

Results

Chromosome 1q gain was significantly associated with shorter OS in both localized cases and the overall cohort, and with inferior EFS specifically in localized patients. In contrast, 16q loss showed no significant prognostic impact. Multivariate analysis confirmed 1q gain as an independent predictor of poor EFS in localized disease. Notably, a higher fraction of genome altered was associated with inferior OS and EFS not only in localized patients but also in the entire cohort, and remained an independent predictor of outcome despite the smaller subset analyzed.

Conclusions

This prospective study validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma. Furthermore, the extent of genomic alteration emerges as a promising predictor of both OS and EFS. Incorporating these biomarkers may improve individualized risk stratification and ultimately enhance patient outcomes.

背景：尤文氏肉瘤是一种罕见的侵袭性肿瘤，主要影响青少年和青壮年。准确的风险分层是治疗的关键，但传统的临床参数缺乏足够的预测准确性。虽然回顾性研究已经确定了潜在的分子生物标志物，但临床实施需要前瞻性验证。方法：国际PROVABES联盟（尤因肉瘤生物标志物的前瞻性验证）旨在评估在国际III期试验中治疗的欧洲患者的分子预后标志物。本研究的重点是305种原发肿瘤的拷贝数改变（CNAs）。用FISH分析组织微阵列中染色体1q增加（n = 297）和16q丢失（n = 266）。在139个样本中使用SNP阵列进一步评估全基因组CNAs。以无事件生存期（EFS）和总生存期（OS）为终点，通过Kaplan-Meier和多变量Cox回归评估与临床结果的相关性。结果：染色体1q增加与局部病例和整体队列中较短的OS显著相关，并与局部患者较低的EFS特异性相关。相比之下，16q的损失对预后没有显著影响。多变量分析证实1q增益是局部疾病EFS差的独立预测因子。值得注意的是，不仅在局部患者中，而且在整个队列中，较高比例的基因组改变与较差的OS和EFS相关，尽管分析的子集较小，但仍然是结果的独立预测因子。结论：本前瞻性研究证实染色体1q增加是局部尤文氏肉瘤预后不良的独立标志。此外，基因组改变的程度是预测OS和EFS的一个很有希望的指标。结合这些生物标志物可以改善个体化的风险分层，最终提高患者的预后。

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引用次数: 0